Chiral sulfur derivatives

Nucleophilic substitution on chiral sulfur derivatives (the so-called Andersen method)... 

New reactions utilizing features of sulfur atom in chiral sulfoxides, derivatives of heterocycles 99YZ126. 

The aldehyde structures and the tosylhydrazone salts were varied in an extensive study of scope and limitations, with use of both achiral and chiral sulfur ylides [73]. Aromatic aldehydes were excellent substrates in the reaction with benzaldehyde-derived ylides, whereas aliphatic aldehydes gave moderate yields and transxis ratios. 

Keywords. Phosphorus and sulfur derivatives, Dithioesters, Hetero Diels-Alder, Sigmatropic rearrangements. Chiral ligands... 

In contrast to the large number of chiral pyridine derivatives used as ligands of metal complexes in asymmetric catalysis, only a few examples of chiral sulfur-containing pyridine ligands have so far been reported, such as pyridine thioethers derived from ( + )-camphor depicted in Scheme 1.33, which were assessed in the test reaction providing enantioselectivities of up to 76% ee. The related 2,2 -bipyridine thioethers were also prepared but showed a lower stereodilferentiating capability in the test reaction. 

Sulfoximines bearing a chiral sulfur atom have recently emerged as valuable ligands for metal-catalysed asymmetric synthesis.In particular, C2-symmetric bis(sulfoximines), such as those depicted in Scheme 1.51, were applied to the test reaction, achieving enantioselectivities of up to 93% ee. The most selective ligand (R = c-Pent, R = Ph) of the series was also applied to the nucleophilic substitution reaction of l,3-diphenyl-2-propenyl acetate with substituted malonates, such as acetamido-derived diethylmalonate, which provided the corresponding product in 89% yield and 98% ee. 

A second class of organometallic derivatives, namely alkyllithium reagents, has been condensed onto aldehydes in the presence of chiral sulfur-containing... 

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

The ORD and CD curves of chiral sulfinamides derived from aromatic sulfinic acids show a strong Cotton effect centered at 240 to 256 nm (83). The position of this Cotton effect, its dependence on the solvent used, and the amplitude reveal a complete analogy with that observed in alkyl aryl sulfoxides and aromatic menthyl sulfin-ates. Thus, the positive sign of the Cotton effect observed in the ORD curves of dextrorotatory sulfinamides is indicative of the (5)-configuration around sulfur in these compounds. 

As the last point in Sect. IV, we discuss briefly the reactions of chiral sulfur compounds with electrophilic reagents. In contrast to nucleophilic substitution reactions, the number of known electrophilic reactions at sulfur is very small and practically limited to chiral tricoordinate sulfur compounds that on reacting with electrophilic reagents produce more stable tetracoordinate derivatives. It is generally assumed that the electrophilic attack is directed on the lone electron pair on sulfur and that the reaction is accompanied by retention of configuration. As typical examples of electrophilic reactions at tricoordinate sulfur, we mention oxidation, imination, alkylation, and halogenation. All these reactions were touched on in the section dealing with the synthesis of chiral tetracoordinate sulfur compounds. 

By reduction of the chiral sulfur moiety to dicoordinate sulfur derivatives. 

The cis- and frans-sulfoxides (551) and (552) have been O-methylated with Meerwein s reagent. Reaction of the methoxy derivative with MeMgBr proceeds with inversion of configuration (Scheme 211) (74JA8026). The stereochemical course of the interconversions of sulfoxide, sulfimide and sulfoximide in the 2,3-dihydrobenzo[6]thiophene series has been investigated (73JA1916). The reaction cycle (Scheme 212) involves both nucleophilic and electrophilic substitution at chiral sulfur. Inversion of configuration takes place in the conversion of (553) to (554) in pyridine. 

A variation of the [C + C=N] pathway involves the addition of sulfur ylides to imines and this method has been effectively used to access a wide range of substituted aziridines under mild reaction conditions. Although high enantiomeric excesses can be achieved by using a chiral sulfur ylide (up to 98%), the m//rstepwise mechanism via a betaine intermediate . Sulfur ylides can be conveniently generated in situ from alkyl halides and chiral sulfides thus, benzyl bromide and tosyl imine in the presence of a camphor-derived chiral sulfide mediator provide aziridine 4 in practically quantitative yield as a 3 1 mixture of /Z-isomers and in 92% ee (A-isomer) (Scheme 8) <2001TL5451>. 

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